Presentation

Birt-Hogg-Dubé syndrome is a rare disorder that affects the skin and increases the risk of certain types of tumors. The condition is characterized by multiple noncancerous tumors of the hair follicles, particularly on the face, neck, and upper chest. These growths typically first appear in a person's twenties or thirties. People with Birt-Hogg-Dubé syndrome also have an increased risk of developing cancerous or noncancerous kidney tumors and possibly tumors in other organs and tissues. Additionally, affected individuals have a higher chance of developing cysts in the lungs and an abnormal collection of air in the chest cavity (pneumothorax) that may result in the collapse of a lung.

Genetics

Mutations in the FLCN gene cause Birt-Hogg-Dubé syndrome.[1] The FLCN gene makes a protein called folliculin. The normal function of this protein is unknown, but researchers believe that it may act as a tumor suppressor. Tumor suppressors normally prevent cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the FLCN gene may interfere with the ability of folliculin to restrain cell growth and division, leading to the formation of noncancerous and cancerous tumors.

Researchers believe that two copies (instead of one copy) of the FLCN gene must be altered for a person to develop the kidney tumors often seen in Birt-Hogg-Dubé syndrome. People with this condition are born with one mutated copy of the FLCN gene in each cell. Then, during their lifetime, the other copy of the gene is mutated in kidney cells. These genetic changes result in no functional copies of the FLCN gene in these cells, allowing the cells to divide uncontrollably and form tumors.